Differences in gene expression in the hippocampus of aged rats associated with better performance in inhibitory avoidance memory formation.

Alterations of long-term declarative memory formation occur to different degrees among individuals during normal aging, but the genetic basis for such differences are not yet fully understood. Aim of the present study was the identification of genes differently expressed in the hippocampus of aged (26-27 month old) rats showing diverse cognitive performance in a single trial inhibitory avoidance (IA) task. IA is a hippocampal-dependent aversive learning, based on contextual fear conditioning. The behavioural paradigm consisted of a training phase in which animals, placed individually in the light compartment of a shock avoidance apparatus, learned to avoid the dark compartment by the delivery of a single, inescapable foot shock (0.6 mA, 2 s) when they accessed it. Rats were tested 3 and 6 hours after the training. According to the performance displayed in the tests, animals were divided into two groups: i) good responders (GR), which obtained retention times above 100s in both tests, and ii) bad responders (BR), which obtained retention times below 100s in both tests. Immediately after the last test, rats were sacrificed, hippocampi were excised and total RNA was extracted. Microarray analysis was performed to identify genes with decreased or increased expression in GR compared to BR rats by using a commercially available chip containing 9715 oligos. We found that the transcription of 43 genes was significantly increased in GR in comparison with BR, including genes functionally linked to signal transduction (e.g. rho family GTPase and dynamin binding protein), translation (e.g. ribosomal protein S6, 60s ribosomal protein L12 and mitochondrial ribosomal protein L41), cell growth and differentiation (e.g. trpc6 and NEL-like 2) energy metabolism (e.g. cytochrome c oxidase subunit VIIb and succinate dehydrogenase 1b) and nucleic acid processing (e.g. U6 small nuclear RNA associated and DEAD box 1). In addition, 18 genes were significantly down-regulated in GR, including genes functionally linked to transcription (e.g. sirtuin 5), apoptosis (e.g. cytochrome c somatic), cell growth and differentiation (e.g. cytidine 5’-triphosphate synthase) and protein transport (e.g. autophagy-related 4B). Present results may provide insight into the mechanisms by which long-term declarative memory formation is maintained in the elderly, and may contribute to the identification of novel targets that can be addressed to ameliorate memory performances.